DEPARTMENT OF RESEARCH
LBH IRB Guide #12: Evaluating and Monitoring Risk in Human Subjects Research Page 1 of 3
Version 3, 05-07-14
Institutional Review Board
Evaluating and Monitoring Risk in Human Subjects Research
Guidelines
This document was designed to assist Institutional Review Board (IRB) members and principal investigators in determining the level of risk and the type of monitoring that will be required for a research study involving human subjects.
A. Risk of Study
The Code of Federal Regulations (45 CFR 46.102(i), 46.111, & 46.406) only defines minimal risk, and defines it as:
“The probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical and psychological examinations or tests.”
The LBH IRB further defines minimal risk and defines other risk levels as follows:
Minimal Risk: Involves no more risk than expected in daily life. There are no serious adverse events anticipated. Examples of minimal risk studies include but are not limited to:
1. Observation studies
2. Behavior studies
3. Nutrition studies
4. Survey/Questionnaire studies
5. Routine psychological testing
6. Anthropomorphic evaluations
7. Exercise testing
8. Oral glucose tolerance tests
9. Intravenous glucose tolerance tests
10. Venipuncture
11. Intravenous catheter insertion
12. EKGs
13. Ultrasound scans
14. DEXA scans
Note: Survey research and questionnaires may present more than minimal risk to subjects if they address highly sensitive information. Inclusion of vulnerable populations (children, prisoners, pregnant women, mentally disabled persons, or economically and/or educationally disadvantaged persons) who may be more sensitive or vulnerable to the risks posed by the research, regardless of the study, may increase the level of risk.
Moderate Risk: Involves risks that are reasonable in relation to anticipated benefits (if any) to subjects and the importance of the knowledge that may reasonably be expected to result. There is a medium to high probability of a moderate-severity event occurring as a result of study participation (e.g., reversible worsening of a non-fatal disease such as seasonal allergy while receiving placebo or pneumonia from a bronchoscopy), but there is adequate surveillance and protections to identify adverse events promptly and to minimize their effects. Examples of moderate risk studies include but are not limited to:
1. Minimal risk studies involving vulnerable populations (e.g. subjects with impaired capacity to give informed consent)
2. Studies involving subjects with serious viral, autoimmune, and malignant illness
3. Studies involving subjects treated with a placebo for a recognized disease
4. Protocols in which there is substantial risk (>5%) of a serious adverse event originating from the underlying condition of the enrolled subject
5. Phase I or II clinical trials with available safety data in humans
6. Industry sponsored phase III clinical trials
7. Studies using drugs for use not indicated
8. Studies that use invasive hemodynamic monitoring with arterial lines
9. Studies in which blood and tissue specimens are stored
10. Studies in which blood and tissue specimens are collected for genetic studies
11. Category II radiation risk [HE (mrem) 500 < HE < 5000 mrem or organ limit of 150/ WT < HT < 750/WT]
High Risk: Involves risks that are greater due to a high probability of an event that is serious and prolonged or permanent occurring as a result of study participation. Examples of high risk studies include but are not limited to:
1. Studies that have potential for high (significant) levels of risk that may result in permanent physical and/or mental changes, hospitalization, and/or death
2. Clinical trials of interventions to prevent or treat diseases that lead to death or irreversible morbidity
3. Phase I or II clinical trials with no available safety data in humans, and blinded Phase II studies
4. Investigator-initiated IND (investigational new drug) or IDE (investigational device exemption) trials
5. Investigator-initiated phase I, II or III clinical trials
6. Investigator-initiated multi-center trials
7. Studies involving an intervention or invasive procedure with substantial risk or potential for severe toxicity
8. Implantation of a device with an IDE
9. FDA-approved agents for non-approved indications
10. The use of a new chemical or drug for which there is little or no toxicology data in humans
11. Clinical trials using investigational agents, gene therapy, or recombinant DNA molecules (gene transfer)
12. Studies involving the manufacturing of agents on campus
13. Studies having has provisions to waive consent in emergency circumstances
14. Category III radiation risk [HE (mrem) > 5000 mrem or organ limit of HT > 750/WT]
Note: A Data Safety Monitoring Board (DSMB) may be required for high risk studies.
B. Monitoring of Study
All protocols presenting the potential of risk to subjects, even minimal risk, should address how the investigator will monitor risk and report adverse events.
Monitoring Recommendations Based on Level of Risk:
Safety monitoring for a protocol must be appropriate for the level of risk identified. The combination of factors used in assessing the level of risk drives the intensity of monitoring required for a protocol. The requirements outlined below represent the minimum amount necessary to assure subject safety. The LBH IRB may require more frequent and/or additional periodic monitoring provided by an IRB Audit Subcommittee. Standard reporting to the IRB of unanticipated problems and adverse events is required regardless of the level of monitoring.
Minimal Intensity Monitoring – The PI or co-investigator will monitor the study with prompt reporting of adverse events and other study related information to the IRB, sponsor, and other agencies as described in the LBH IRB Guide # 3: Adverse Event Reporting. A Modified Safety Monitoring Plan that describes appropriate safety-monitoring procedures will be reviewed and approved by the LBH IRB.
Low Intensity Monitoring –The PI or co-investigator will monitor the study with prompt reporting of adverse events and other study related information to the IRB, sponsor, and other agencies as described in the LBH IRB Guide # 3: Adverse Event Reporting. Team meetings by the PI and his/her staff will be conducted on a routine basis to discuss protocol issues and review adverse events. The Safety Monitoring Plan approved by the LBH IRB will be revised and updated if the risk/benefit ratio changes.
Moderate Intensity Monitoring – The PI or co-investigator monitors the study on a day-to-day basis and includes all monitoring activities described above in low intensity monitoring. In addition, most protocols will require well-described criteria for dose escalation, criteria defining maximum tolerated dose (MTD), and/or criteria for stopping the trial or involvement of a subject. Surveillance and protections are in place to adequately identify adverse events promptly. An independent medical monitor or safety monitoring committee may also be utilized to review adverse events as they occur and make recommendations to the protocol team.
High Intensity Monitoring – The PI or co-investigator monitors the study on a day-to-day basis and includes all monitoring activities described above under Low Intensity Monitoring. Most high-risk protocols will also require a Data Safety Monitoring Committee (DSMC) to monitor the safety and efficacy of the study. An independent Data Safety Monitoring Board (DSMB) is required by NIH Guidelines for all Phase III clinical trials. Based on the level of risk, the complexity of the protocol, and the patient population, the LBH IRB may determine that a clinical trial or protocol requires an independent DSMB or DSMC. Some single institution, investigator initiated, clinical trials or protocols deemed of significant risk may also fit these criteria. If no other DSMB is in place for a single institution clinical trial, the PI may ask the LBH IRB to appoint an independent board to fulfill this function.
LBH IRB Guide #12: Evaluating and Monitoring Risk in Human Subjects Research Page 1 of 3
Version 3, 05-07-14